Substituted pyrimido[1,2-b]pyridazines as positive allosteric modulators of the muscarinic acetylcholine receptor M4

Abstract

Disclosed herein are analogues of 6-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine, i.e. 7-(4-((phenyl or pyridin-3-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one derivatives of formula (I) which may be useful as positive allosteric modulators of the muscarinic acetylcholine receptor M4 (mAChR M4). Also disclosed herein are methods of making the compounds, pharmaceutical compositions comprising the compounds, and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions.

What is claimed is: 
     
       1. A compound of formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof, 
         wherein:
 R 1  is H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, C 1 -C 4  hydroxyalkyl, -L 1 -OR a , -L 1 -C 3 -C 6  cycloalkyl, OR a , or C 3 -C 6  cycloalkyl; 
 L 1  is —C 1 -C 3  alkylene-; 
 R a  is C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, or C 3 -C 6  cycloalkyl; 
 R 2  is H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L 2 -OR b , NHR b , NR b R b , OR b , or C 3 -C 6  cycloalkyl; 
 R 7  is H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L 2 -OR b , NHR b , NR b R b , OR b , or C 3 -C 6  cycloalkyl; 
 each L 2  is independently —C 1 -C 3  alkylene-; 
 each R b  is independently C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, or C 3 -C 6  cycloalkyl; or 
 any two R b , taken together with the nitrogen atom to which they are attached, independently forms a monocyclic 4- to 7-membered heterocyclyl, wherein the 4- to 7-membered heterocyclyl is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halo, C 1 -C 4  alkyl, and C 1 -C 4  haloalkyl; 
 R 3  is H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L 3 -OR c , OR c , or C 3 -C 6  cycloalkyl; 
 L 3  is —C 1 -C 3  alkylene-; 
 R c  is C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, or C 3 -C 6  cycloalkyl; 
 each R 4  is independently halo, C 1 -C 4  alkyl, -L 4 -OR d , or OR d ; 
 each L 4  is independently —C 1 -C 3  alkylene-; 
 each R d  is independently C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, or C 3 -C 6  cycloalkyl; 
 X is CR 5 , or N; 
 R 5a  is H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L 5 -OR e , OR e , or C 3 -C 6  cycloalkyl; 
 each R 5  is independently halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L 5 -OR e , OR e , C 3 -C 6  cycloalkyl, phenyl, or 5- or 6-membered heteroaryl; 
 each L 5  is independently —C 1 -C 3  alkylene-; 
 each R e  is independently C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, or C 3 -C 6  cycloalkyl; or 
 two R 5 , taken together with the carbon atoms to which they are attached, form a fused monocyclic 5- to 8-membered heterocycle;
 wherein the 5- to 8-membered heterocycle contains one or two heteroatoms independently selected from the group consisting of N, O, and S; and 
 wherein the 5- to 8-membered heterocycle is optionally substituted with 1, 2, 3, or 4 independently selected R 6  substituents; 
 
 each R 6  is independently halo, C 1 -C 4  alkyl, -L 6 -OR f , OR f , or ═O; 
 each L 6  is independently —C 1 -C 3  alkylene-; 
 each R f  is independently C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, or C 3 -C 6  cycloalkyl; 
 each R 5b  is independently halo, CN, C 1 -C 2  alkyl, C 1 -C 2  fluoroalkyl, OC 1 -C 2  alkyl, OC 1 -C 2  fluoroalkyl, or C 3 -C 4  cycloalkyl; 
 m is 0, 1, or 2; 
 n is 0, 1, or 2; and 
 o is 0, 1, or 2. 
 
       
     
     
       2. The compound of  claim 1 , wherein the compound is of formula (I-A): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof, 
         wherein:
 each R 5c  is independently H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L 5 -OR c , OR c , C 3 -C 6  cycloalkyl, phenyl, or 5- or 6-membered heteroaryl; or 
 two R 5c , taken together with the carbon atoms to which they are attached, form a fused monocyclic 5- to 8-membered heterocycle;
 wherein the 5- to 8-membered heterocycle contains one or two heteroatoms independently selected from the group consisting of N, O, and S; and 
 wherein the 5- to 8-membered heterocycle is optionally substituted with 1, 2, 3, or 4 independently selected R 6  substituents. 
 
 
       
     
     
       3. The compound of  claim 2 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 5c  is independently H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L-OR e , OR e , phenyl, or 5- or 6-membered heteroaryl. 
     
     
       4. The compound of  claim 3 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 5c  is independently H, halo, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L-OR e , or OR e . 
     
     
       5. The compound of  claim 4 , wherein the compound is of formula (I-B): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof, 
         wherein:
 G 1  is: 
 
       
       
         
           
           
               
               
           
         
       
     
     
       6. The compound of  claim 5 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein G 1  is: 
       
         
           
           
               
               
           
         
       
     
     
       7. The compound of  claim 6  or a pharmaceutically acceptable salt or stereoisomer thereof, wherein G 1  is: 
       
         
           
           
               
               
           
         
       
     
     
       8. The compound of  claim 2 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein two R 5c , taken together with the carbon atoms to which they are attached, form a fused monocyclic 5- to 8-membered heterocycle;
 wherein the 5- to 8-membered heterocycle contains one or two heteroatoms independently selected from the group consisting of N, O, and S; and 
 wherein the 5- to 8-membered heterocycle is optionally substituted with 1, 2, 3, or 4 independently selected R 6  substituents. 
 
     
     
       9. The compound of  claim 8 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein two R 5c , taken together with the carbon atoms to which they are attached, form a fused monocyclic 5- to 8-membered heterocycle;
 wherein the 5- to 8-membered heterocycle contains one or two heteroatoms independently selected from the group consisting of N and O; and 
 wherein the 5- to 8-membered heterocycle is optionally substituted with 1 or 2 independently selected R 6  substituents. 
 
     
     
       10. The compound of  claim 1 , wherein the compound is of formula (I-B): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof, 
         wherein:
 G 1  is: 
 
       
       
         
           
           
               
               
           
         
         
           q is 0, 1, 2, 3, or 4. 
         
       
     
     
       11. The compound of  claim 10 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
 G 1  is: 
 
       
         
           
           
               
               
           
         
         R 5a  is H, halo, or C 1 -C 4  alkyl. 
       
     
     
       12. The compound of  claim 11 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein G 1  is: 
       
         
           
           
               
               
           
         
       
     
     
       13. The compound of  claim 1 , wherein the compound is of formula (Ia): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof. 
       
     
     
       14. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1  is H, C 1 -C 4  alkyl, C 1 -C 4  haloalkyl, -L 1 -OR a , -L 1 -C 3 -C 6  cycloalkyl, or C 3 -C 6  cycloalkyl. 
     
     
       15. The compound of  claim 14 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1  is H. 
     
     
       16. The compound of  claim 14 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1  is C 1 -C 4  alkyl. 
     
     
       17. The compound of  claim 14 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1  is C 1 -C 4  fluoroalkyl. 
     
     
       18. The compound of  claim 17 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1  is CHF 2 . 
     
     
       19. The compound of  claim 17 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 1  is CF 3 . 
     
     
       20. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2  is H, C 1 -C 4  alkyl, -L 2 -OR b , NHR b , NR b R b , OR b , or C 3 -C 6  cycloalkyl. 
     
     
       21. The compound of  claim 20 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2  is H. 
     
     
       22. The compound of  claim 20 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2  is C 1 -C 4  alkyl. 
     
     
       23. The compound of  claim 20 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 2  is CH 3 . 
     
     
       24. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7  is H, halo, C 1 -C 4  alkyl, NR b R b , or C 3 -C 6  cycloalkyl. 
     
     
       25. The compound of  claim 24 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7  is H, F, Cl, CH 3 , azetidin-1-yl, or cyclopropyl. 
     
     
       26. The compound of  claim 25 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 7  is H. 
     
     
       27. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3  is H, C 1 -C 4  alkyl, -L 3 -OR c , or C 3 -C 6  cycloalkyl. 
     
     
       28. The compound of  claim 27 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3  is C 1 -C 4  alkyl. 
     
     
       29. The compound of  claim 28 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 3  is CH 3 . 
     
     
       30. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein each R 4  is independently halo or C 1 -C 4  alkyl. 
     
     
       31. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein X is CR 5a . 
     
     
       32. The compound of  claim 31 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R 5a  is H. 
     
     
       33. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein X is N. 
     
     
       34. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein n is 0. 
     
     
       35. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein o is 0. 
     
     
       36. The compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof, wherein o is 1. 
     
     
       37. The compound of  claim 1 , or a stereoisomer thereof, wherein the compound, or stereoisomer thereof, is selected from the group consisting of:
 8-methyl-7-(4-((6-methylpyridin-3-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-(4-fluorophenoxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 3-chloro-7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-fluoropiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3S,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-fluoropiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(3R,4S)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-fluoropiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3S,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-fluoropiperidin-1-yl)-2,8-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(3R,4S)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-fluoropiperidin-1-yl)-2,8-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-fluoropiperidin-1-yl)-3-fluoro-2,8-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3S,4S)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-fluoropiperidin-1-yl)-3-fluoro-2,8-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2,8-dimethyl-7-(4-((6-methylpyridin-3-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-(benzo[d][1,3]dioxol-5-yloxy)-3-fluoropiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-3-fluoro-4-(isochroman-6-yloxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)oxy)-3-fluoropiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-((2,3-dihydrobenzofuran-5-yl)oxy)-3-fluoropiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-(chroman-7-yloxy)-3-fluoropiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2,8-dimethyl-7-(4-((1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2,8-dimethyl-7-(4-((2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2,8-dimethyl-7-(4-((2-methyl-1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((6-methoxy-5-methylpyridin-3-yl)oxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((6-(methoxymethyl)pyridin-3-yloxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 8,9-dimethyl-7-(4-(p-tolyloxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2-(difluoromethyl)-8,9-dimethyl-7-(4-((6-methylpyridin-3-yloxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-(4-chlorophenoxy)piperidin-1-yl)-2-(difluoromethyl)-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 8,9-dimethyl-7-(4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2-(difluoromethyl)-8,9-dimethyl-7-(4-(4-(trifluoromethyl)phenoxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2,8-dimethyl-7-(4-((1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)oxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-(4-fluorophenoxy)piperidin-1-yl)-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2-(difluoromethyl)-7-(4-(4-fluorophenoxy)piperidin-1-yl)-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 2-(difluoromethyl)-8,9-dimethyl-7-(4-(p-tolyloxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 8,9-dimethyl-7-(4-((6-methylpyridin-3-yloxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-(4-chlorophenoxy)piperidin-1-yl)-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-(3-fluoro-4-methylphenoxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-(4-ethylphenoxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-(4-isopropylphenoxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 8-methyl-7-(4-(4-propylphenoxy)piperidin-1-yl)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((6-(methoxymethyl)-5-methylpyridin-3-yl)oxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-2-ethyl-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-2-isopropyl-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-2-(methoxymethyl)-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 8-cyclopropyl-7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-9-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 9-cyclopropyl-7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yloxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((2S,4S)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-2-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((2S,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-2-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((2R,4S)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-2-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4S)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((3R,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-3-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((2R,4R)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-2-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-8-methyl-9-(methylamino)-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-9-methoxy-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 9-(azetidin-1-yl)-7-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yloxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((2R,4S)-4-((8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-2-methylpiperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one; 
 7-((2R,4S)-4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)-2-methylpiperidin-1-yl)-8,9-dimethyl-4H-pyrimido[1,2-b]pyridazin-4-one; and 
 7-(4-((8-fluoro-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidin-1-yl)-8-methyl-4H-pyrimido[1,2-b]pyridazin-4-one, 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
       38. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof. 
     
     
       39. A method for modulating muscarinic acetylcholine receptor (mAChR) M 4  activity in a patient in need thereof, wherein the method comprises administering to the patient a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt or stereoisomer thereof. 
     
     
       40. The method of  claim 39 , wherein the patient has a neurological disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction or a psychiatric disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction. 
     
     
       41. The method of  claim 40 , wherein the neurological disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction or psychiatric disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction is selected from the group consisting of an autistic disorder, a behavioral manifestation of mental retardation, a bipolar disorder, a cognitive disorder, a disruptive behavior disorder, a memory disorder, a movement disorder, and psychosis. 
     
     
       42. The method of  claim 40 , wherein the neurological disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction or psychiatric disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction is selected from the group consisting of Alzheimer's disease, bipolar disorder, borderline personality disorder, Huntington's disease, a pain disorder, schizophrenia, and a sleep disorder. 
     
     
       43. The method of  claim 40 , wherein the neurological disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction or psychiatric disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction is selected from the group consisting of akinetic-rigid syndrome, a drug induced and neurodegeneration-based dyskinesia, a movement disorder associated with Parkinson's disease, tardive dyskinesia, and Tourette's syndrome. 
     
     
       44. The method of  claim 40 , wherein the neurological disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction or psychiatric disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction is selected from the group consisting of anxiety associated with psychosis, a mood disorder associated with a psychotic disorder, a mood disorder associated with schizophrenia, a psychotic episode of anxiety, and schizophrenia. 
     
     
       45. The method of  claim 40 , wherein the neurological disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction or psychiatric disorder associated with muscarinic acetylcholine receptor (mAChR) M 4  dysfunction is attention deficit hyperactivity disorder or dementia.